The relative effect of glucose and lipids on whole-body protein-metabolism kinetics was assessed in seven infants undergoing parenteral feeding. Protein intake was kept constant and nonprotein energy was either provided as glucose alone or as an isoenergetic glucose-lipid mixture according to a randomized crossover trial. Protein metabolism and energy-substrate utilization were assessed by a primed, constant L-[13C]leucine infusion, combined with indirect calorimetry. There was a significant difference in the pattern of energy-substrate utilization according to regime. Protein turnover (11.3 +/- 0.7 vs 9.8 +/- 0.4 g.kg-1.d-1; P less than 0.05), protein breakdown (8.4 +/- 0.6 vs 7.1 +/- 0.4 g.kg-1.d-1; P less than 0.05), and amino acid oxidation rates (2.7 +/- 0.4 vs 1.4 +/- 0.5 g.kg-1.d-1; P less than 0.05) were higher for the glucose than the glucose-lipid treatment, whereas protein-synthesis rates did not significantly differ. These results suggest that the nature of energy substrates delivered to parenterally fed infants may affect protein metabolism.